Interventional Study in Adults With Immune Thrombocytopenia Purpura (ITP) Receiving Romiplostim

A Phase 2 Interventional Single Arm Study Describing Platelet Responses and ITP Remission Rates in Adult Subjects With Immune Thrombocytopenia Purpura Receiving Romiplostim

The purpose of this study is to describe the number of months with a platelet response over a 12 month treatment period and to describe ITP remission rates in adults with ITP receiving romiplostim.

Study Overview

• Status: Completed
• Conditions: Idiopathic Thrombocytopenic Purpura
• Intervention / Treatment: Biological: Romiplostim

Detailed Description

The study includes a 4-week screening period, a 12-month romiplostim treatment period, and a romiplostim dose-tapering period.

During the 12-month treatment period romiplostim doses could be increased or decreased to maintain a platelet count between ≥ 50 x 10^9/L and ≤ 200 x 10^9/L. Participants who dose reduce such that they no longer require treatment with romiplostim during the 12-month treatment period will continue with all required study procedures up to 12 months and will be monitored for ITP remission for at least 6 months.

At the completion of the 12-month treatment period, participants receiving only romiplostim and with a platelet count ≥ 50 x 10^9/L will enter the tapering period, during which the romiplostim dose will be decreased by 1 µg/kg every 2 weeks, for up to 19 weeks. If a participant maintains a platelet count of ≥ 50 x 10^9/L in the absence of romiplostim and all medications for ITP (concomitant or rescue), the participant will be followed for at least 6 months to confirm the incidence of ITP remission. If a participant's platelet count falls below 50 x 10^9/L and the participant has tapered off treatment with romiplostim, the participant will enter the stabilization period and reinitiate romiplostim for up to 8 weeks.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Research Site
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Research Site
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Research Site
• Czechia
  • Brno, Czechia, 625 00
    • Research Site
  • Ostrava-Poruba, Czechia, 708 52
    • Research Site
  • Praha 10, Czechia, 100 34
    • Research Site
  • Praha 2, Czechia, 128 08
    • Research Site
  • Praha 2, Czechia, 128 20
    • Research Site
• France
  • Bondy Cedex, France, 93143
    • Research Site
  • Créteil Cedex, France, 94010
    • Research Site
  • Dijon, France, 21000
    • Research Site
  • Pessac Cedex, France, 33604
    • Research Site
  • Toulouse Cedex 9, France, 31059
    • Research Site
• Germany
  • Dresden, Germany, 01307
    • Research Site
  • Duisburg, Germany, 47166
    • Research Site
  • Düsseldorf, Germany, 40479
    • Research Site
  • Köln, Germany, 50674
    • Research Site
• Italy
  • Bari, Italy, 70124
    • Research Site
  • Catania, Italy, 95124
    • Research Site
  • Monza (MB), Italy, 20900
    • Research Site
  • Napoli, Italy, 80131
    • Research Site
  • Novara, Italy, 28100
    • Research Site
  • Roma, Italy, 00161
    • Research Site
  • San Giovanni Rotondo FG, Italy, 71013
    • Research Site
  • Vicenza, Italy, 36100
    • Research Site
• Poland
  • Gdansk, Poland, 80-952
    • Research Site
  • Katowice, Poland, 40-032
    • Research Site
  • Lublin, Poland, 20-080
    • Research Site
  • Poznan, Poland, 61-505
    • Research Site
  • Wroclaw, Poland, 50-367
    • Research Site
• Spain
  • Andalucía
    • Málaga, Andalucía, Spain, 29010
      • Research Site
  • Cataluña
    • Barcelona, Cataluña, Spain, 08035
      • Research Site
  • Galicia
    • A Coruña, Galicia, Spain, 15006
      • Research Site
  • Madrid
    • Alcorcon, Madrid, Spain, 28922
      • Research Site
    • Majadahonda, Madrid, Spain, 28222
      • Research Site
• United Kingdom
  • Coventry, United Kingdom, CV2 2DX
    • Research Site
  • Leeds, United Kingdom, LS9 7TF
    • Research Site
  • London, United Kingdom, SW17 0QT
    • Research Site
  • London, United Kingdom, E1 2ES
    • Research Site
  • Oxford, United Kingdom, OX3 9DU
    • Research Site
• United States
  • California
    • Anaheim, California, United States, 92801
      • Research Site
    • Orange, California, United States, 92868
      • Research Site
  • Florida
    • Boynton Beach, Florida, United States, 33435
      • Research Site
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Research Site
  • North Carolina
    • Hickory, North Carolina, United States, 28602
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Research Site
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Research Site
  • Virginia
    • Richlands, Virginia, United States, 24641
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

- Subject has been diagnosed with primary ITP according to the American Society of Hematology (ASH) guidelines (George et al, 1996) and previously received only 1st line therapies.

First line therapy is defined as corticosteroids, immunoglobulin G (IVIG), anti-D and vinca alkaloids (used for the treatment of ITP related thrombocytopenia only). A platelet transfusion at any time during the six month period since the original diagnosis would not exclude the subject from study participation

• Initial diagnosis of primary ITP within 6 months of enrollment
• Age ≥ 18 years at screening
• A single platelet count ≤ 30 x 10⁹/L at any time during the screening period
• Subject or subject's legally acceptable representative has provided informed consent

Exclusion Criteria:

• Known history of a bone marrow stem cell disorder
• Surgical resection of the spleen
• Subject has a history of cancer or current malignancy other than basal cell carcinoma or cervical cancer in-situ with active treatment or disease within 5 years of screening
• Known history of congenital thrombocytopenia
• Known history of hepatitis B, hepatitis C, or human immunodeficiency virus
• Positive H. pylori by urea breath test or stool antigen test at screening
• Known history of systemic lupus erythematosus, Evans syndrome, or autoimmune neutropenia
• Known history of antiphospholipid antibody syndrome or positive for lupus anticoagulant
• Known history of disseminated intravascular coagulation, hemolytic uremic syndrome, or thrombotic thrombocytopenic purpura
• Previous history of recurrent venous thromboembolism or thrombotic events or an occurrence within 5 years of enrollment.
• Previous use of romiplostim, pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), eltrombopag, recombinant human thrombopoietin (rHuTPO) or any platelet producing agent
• Rituximab (for any indication) or mercaptopurine (6-MP) or anticipated use during the time of the proposed study
• All hematopoietic growth factors including interleukin-11 (IL-11) (oprelvekin) within 4 weeks before the screening visit
• Alkylating agents use at any time before or during the screening visit or anticipated during the time of the proposed study
• Known hypersensitivity to any recombinant E. coli-derived product (eg, Infergen, Neupogen, Somatropin, and Actimmune)
• Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational agent(s)
• Subject will have any other investigational procedures performed while enrolled in this clinical study
• Subject is pregnant or breast feeding, or planning to become pregnant within 5 weeks after the end of treatment
• Female subject of child bearing potential is not willing to use, in combination with her partner, highly effective contraception during treatment and for 4 weeks after the end of treatment
• Subject has previously enrolled into a romiplostim study
• Subject will not be available for protocol required study visits, to the best of the subject's and investigator's knowledge
• Subject has any kind of disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Romiplostim; Participants received romiplostim administered weekly by subcutaneous injection during the 12-month treatment period. The starting dose was 1 μg/kg with weekly dose increases continued in increments of 1 μg/kg/week to a maximum dose of 10 μg/kg in an attempt to reach a target platelet count of ≥ 50 x 10^9/L.	Biological: Romiplostim; Romiplostim will be administered weekly by subcutaneous injection; Other Names: Nplate; AMG 531

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Months With Platelet Response During the 12-Month Treatment Period	The primary endpoint was the number of months a participant achieved a platelet response during the 12-month treatment period. A platelet response for any 1 month was defined as the median of platelet counts measured in the month ≥ 50 x 10^9/L. Platelet counts within 4 weeks following a rescue medication use or following splenectomy were considered non-response. Months without any platelet count measurement were considered as months with no platelet response.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With ITP Remission	ITP remission was defined as maintaining every platelet count ≥ 50 x 10^9/L for at least 6 months in the absence of romiplostim and any other therapies to treat ITP.	Up to 24 months
Percentage of Participants With Splenectomy During the 12-month Treatment Period	If treatment with romiplostim was deemed ineffective or intolerable by the investigator, a splenectomy may have been performed.	12 months
Number of Participants With Adverse Events	An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. The event does not necessarily have a causal relationship with study treatment. A serious adverse event is defined as an adverse event that meets at least one of the following serious criteria: • fatal • life threatening • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • congenital anomaly/birth defect • other significant medical hazard. Whether an adverse event was treatment-related (TRAE) or not was determined by investigator.	From first dose date of romiplostim to end of study (up to 24 months).
Number of Participants Who Developed Antibodies to Romiplostim	The number of participants who developed antibody formation (defined as negative at baseline and positive at post-baseline, transient or persistent) to romiplostim, endogenous thrombopoietin (eTPO), and thrombopoietin mimetic peptide (TMP, the peptide component of romiplostim) was summarized.	Baseline and at end of treatment (based on response to treatment, this could occur between 12 months and approximately 18 months)

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Cines DB, Wasser J, Rodeghiero F, Chong BH, Steurer M, Provan D, Lyons R, Garcia-Chavez J, Carpenter N, Wang X, Eisen M. Safety and efficacy of romiplostim in splenectomized and nonsplenectomized patients with primary immune thrombocytopenia. Haematologica. 2017 Aug;102(8):1342-1351. doi: 10.3324/haematol.2016.161968. Epub 2017 Apr 14.
• Kuter DJ, Newland A, Chong BH, Rodeghiero F, Romero MT, Pabinger I, Chen Y, Wang K, Mehta B, Eisen M. Romiplostim in adult patients with newly diagnosed or persistent immune thrombocytopenia (ITP) for up to 1 year and in those with chronic ITP for more than 1 year: a subgroup analysis of integrated data from completed romiplostim studies. Br J Haematol. 2019 May;185(3):503-513. doi: 10.1111/bjh.15803. Epub 2019 Feb 21.
• Kuter DJ, Arnold DM, Rodeghiero F, Janssens A, Selleslag D, Bird R, Newland A, Mayer J, Wang K, Olie R. Safety and efficacy of self-administered romiplostim in patients with immune thrombocytopenia: Results of an integrated database of five clinical trials. Am J Hematol. 2020 Jun;95(6):643-651. doi: 10.1002/ajh.25776. Epub 2020 Mar 21.
• Newland A, Godeau B, Priego V, Viallard JF, Lopez Fernandez MF, Orejudos A, Eisen M. Remission and platelet responses with romiplostim in primary immune thrombocytopenia: final results from a phase 2 study. Br J Haematol. 2016 Jan;172(2):262-73. doi: 10.1111/bjh.13827. Epub 2015 Nov 5.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2010
• Primary Completion (Actual): September 20, 2013
• Study Completion (Actual): December 26, 2013

Study Registration Dates

• First Submitted: June 10, 2010
• First Submitted That Met QC Criteria: June 10, 2010
• First Posted (Estimate): June 14, 2010

Study Record Updates

• Last Update Posted (Actual): September 21, 2022
• Last Update Submitted That Met QC Criteria: September 8, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: ITP
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Blood Coagulation Disorders; Skin Manifestations; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura; Purpura, Thrombocytopenic; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia
• Other Study ID Numbers: 20080435; 2010-019987-35 (EudraCT Number)